Psychedelics and the Serotonin Hypothesis of Eating Disorders

Serotonergic psychedelics, especially 5-HT2A receptor agonists like psilocybin, show potential for treating eating disorders such as anorexia nervosa, bulimia nervosa, and binge eating disorder. The review connects these interventions to the serotonin hypothesis of eating disorders, highlighting serotonergic dysregulation and impaired cognitive flexibility as core features. Psychedelics may promote neuroplasticity and psychological insight through 5-HT2A signaling modulation, based on animal models, human neuroimaging, and early clinical trials. Preliminary open-label studies suggest psilocybin can improve eating disorder symptoms and quality of life, though evidence remains early and methodologically limited. The authors conclude that further controlled trials are needed, but psychedelics represent a novel mechanistic approach to entrenched eating disorder psychopathology.

Study at a glance

Abstract

Recent advances in psychedelic research have renewed interest in their therapeutic potential for psychiatric disorders characterized by cognitive and behavioral rigidity. This review examines the rationale for using serotonergic psychedelics—particularly 5-HT2A receptor agonists such as psilocybin—in the treatment of eating disorders (EDs), including anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED). The paper contextualizes these interventions within the broader serotonin hypothesis of EDs, emphasizing serotonergic dysregulation and impaired cognitive flexibility as central features of these conditions. Drawing from animal models, human neuroimaging studies, and emerging clinical trials, the authors outline how psychedelics may promote neuroplasticity and psychological insight through modulation of 5-HT2A signaling. Preliminary evidence from open-label studies suggests psilocybin may improve ED symptoms and quality of life, though findings are early and methodologically limited. The paper also reviews data on ayahuasca, MDMA, and non-psychedelic serotonergic agents, highlighting both the promise and complexity of psychedelic-assisted therapy in EDs. The authors conclude that while further controlled trials are needed to clarify efficacy, safety, and optimal treatment parameters, psychedelics offer a novel, mechanistically distinct avenue for addressing entrenched ED psychopathology.